This study conducted by researchers from Vigo presents an innovative sequential therapeutic strategy against pancreatic ductal adenocarcinoma, one of the most lethal cancers due to its stromal barrier that prevents drug penetration.
The novelty lies in the biphasic and sequential treatment: first, lipid nanoparticles containing siRNA that silence the transcription factors YAP1 and FOSL1 are administered, weakening the tumor’s protective stroma; then combination chemotherapy (entinostat and gemcitabine) is applied, which penetrates more effectively into the now permeable tumor tissue.
Results in preclinical models (mouse xenografts and patient organoids) demonstrated reduced fibrotic tissue, increased drug penetration and superior therapeutic efficacy. This approach represents a paradigm shift from traditional combination therapies.
Immacolata Maietta, Patricia Domínguez Arístegui, Iban González Álvarez, Omayra Rodríguez Atanes, Eva María García Fontán, Susana Teijeira Bautista, África González-Fernández, Rosana Simón-Vázquez, Sequential YAP1/FOSL1 silencing and epigenetic therapy to overcome stromal barriers in pancreatic cancer, International Journal of Pharmaceutics, 2025, vol. 684, 126155. https://doi.org/10.1016/j.ijpharm.2025.126155.
